5-HTTLPR polymorphism, mood disorders and MDMA use in a 3-year follow-up study.

A 3-year longitudinal prospective study was conducted to compare the incidence of substance use disorders (SUD) and non-substance use disorders (NSUD) among ecstasy users and two control groups: one of cannabis users and the other of non-drug users. The 5-HTTLPR polymorphism related to NSUD was also studied. A total of 94 subjects were included: 37 ecstasy users, 23 cannabis users and 34 non-drug users. SUD and NSUD disorders were diagnosed according to the fourth edition of the Diagnostic and Statistical Manual of Mental Health Disorders criteria using the Psychiatric Research Interview for Substance and Mental Disorders. Incidence Rates (IR) are presented. The 5-HTTLPR polymorphism was analyzed. Hardy-Weinberg equilibrium was studied. The results of the study showed that the highest IR of SUD was cannabis abuse/dependence in both the ecstasy (IR: 48.6/100 person-year) and cannabis (IR: 2.5/100 person-year) groups. There were no new cases of SUD in non-drug users at follow-up. The highest IR of NSUD was primary mood disorder in both the ecstasy (IR: 4.2/100 person-year) and in the non-drug (IR: 1.3/100 person-year) groups (P < 0.282). There were no new cases of NSUD in the cannabis group at follow-up. 5-HTTLPR polymorphism was associated with lifetime of primary mood disorders in ecstasy group (P = 0.018). Ecstasy use was associated with a higher rate of cannabis abuse/dependence disorders and mood disorders than cannabis use. In the ecstasy users, 5-HTTLPR polymorphism may result in a high vulnerability to primary mood disorders.

Auditory event-related potentials (P3) and cognitive performance in recreational ecstasy polydrug users: evidence from a 12-month longitudinal study.

RATIONALE: There is important preclinical evidence of the long-lasting neurotoxic and selective effects of ecstasy (MDMA) on serotonin systems in nonhuman primates. In humans, long-term recreational use of ecstasy has been mainly associated with memory impairment. OBJECTIVE: The first aim of our study was to evaluate the cognitive and electrophysiological long-term alterations associated with lifetime ecstasy use within a sample of ecstasy polydrug users along a 1-year follow-up. Our second aim was to explore the relationship between specific cognitive functions and P300 (P3) event-related potentials (ERPs) in ecstasy users. MATERIALS AND METHODS: We conducted auditory P3 latency and amplitude and administered a battery of cognitive tests to three groups of subjects: 14 current ecstasy polydrug users, 13 current cannabis users, and 22 controls free of illicit drugs in two evaluations during 1 year. RESULTS: We found significant differences between ecstasy users and controls on cognitive measures of word fluency, processing speed, and memory recognition after 1-year follow-up. We found no significant differences between ecstasy and cannabis users or cannabis users and controls on cognitive tests. Lifetime ecstasy use was associated with poorer memory recognition. No group differences were shown on P3 latency or amplitude. Significant correlations emerged between P3 latency and cannabis lifetime use (higher cannabis use was related to faster latency, showing a paradoxical effect) but not with ecstasy exposure. CONCLUSIONS: Our findings provide evidence of mild long-term cognitive deficits among ecstasy polydrug users. Both ecstasy use and the dynamic interaction between ecstasy and cannabis effects may account for these deficits. No significant P3 alterations were found in ecstasy users.

Combined immunomodulating properties of 3,4-methylenedioxymethamphetamine (MDMA) and cannabis in humans.

AIMS: Cell-mediated immune function and the occurrence of mild infectious diseases was investigated. Participants Polydrug consumers of 3,4-methylenedioxymethamphetamine (MDMA) and cannabis (n = 37) compared to cannabis users only (n = 23) and control group (n = 34). DESIGN: A longitudinal prospective study with three cross-sectional evaluations at time 0 and at 6 months and 1 year was performed. FINDINGS: At baseline, a significant decrease in interleukin (IL)-2 and an increase in anti-inflammatory transforming growth factor (TGF)-beta1, together with a decrease in the number of total lymphocytes, CD4 and natural killer (NK) cells were observed in the MDMA-cannabis group, with intermediate alterations in the cannabis group. Immune alterations observed at baseline were sustained over time. No differences were found between regular and occasional MDMA users. A significantly higher rate of mild infections in regular MDMA-cannabis users compared with occasional MDMA-cannabis users and the remaining groups was observed. CONCLUSIONS: The present data confirm that long-term alterations in immunological homeostasis may result in general health status impairment and subsequent increased susceptibility to infection and immune-related disorders.

Development and validation of a gas chromatography-mass spectrometry assay for hair analysis of amphetamine, methamphetamine and methylenedioxy derivatives.

A procedure based on gas chromatography-mass spectrometry (GC-MS) is described for the determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), 3,4-methylenedioxyethylamphetamine (MDE or MDEA) and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in hair. Hair samples were digested with 1 M sodium sulfide at 37 degrees C (by shaking for 3 h and was kept at room temperature overnight), and extracted with two sequential extraction procedures: liquid-liquid extraction with tert-butyl methyl ether and solid-phase extraction with Bond-Elut Certify columns. Extracted analytes were derivatised with N-methyl-bis(trifluoroacetamide), separated by a 5% phenylmethylsilicone column and determined by a mass spectrometer detector in selected ion monitoring mode. A good reproducibility (intra-assay R.S.D.=1.5-15.7%), accuracy (intra-assay error = 2.0-11.7%) and sensitivity (LOD=0.03-0.08 ng/mg hair) were attained. The method was successfully applied to the analysis of the proximal (1 cm) hair segment to assess recent self-reported use in "ecstasy" consumers. Otherwise, further studies are needed to validate methodology developed in case of amphetamine consumption.

Assessment of chronic exposure to MDMA in a group of consumers by segmental hair analysis.

The suitability of segmental hair analysis of MDMA to monitor past chronic exposure to the drug was investigated in a follow-up study of ecstasy consumers. The purpose, among others, was to look for an objective biomarker of the history of drug consumption. Thirteen naturally colored hair samples were used to assess possible association between hair concentration of MDMA in 1-, 5-, and 9-cm segments and self-reported use in the last 1, 6, and 12 months. Agreement between the self-reported data given by the subjects on their "ecstasy" use in the previous month and MDMA hair concentration was good (r = 0.92) in all the examined subjects, with the exception of 2 individuals who declared a high consumption of the drug (12 tablets in the last month). When comparing the subjects' declaration of tablets consumed per month within the last 6 months, concordance with the hair MDMA values decreased and no correlation seemed to exist between the mean number of tablets consumed in the last 12 months and the concentration of MDMA in hair. However, when grouping subjects with a similar level of declared drug use (independently of whether in the previous month, last 6 months and last 12 months) and comparing the data with the mean MDMA concentrations found in the corresponding hair segments, an excellent level of agreement was found in groups of subjects consuming <5 tablets of MDMA per month (r = 0.93). Although the present findings were obtained from a small group of individuals and are intended as preliminary results, we can conclude that a cutoff of 0.5 ng MDMA per mg hair seems reasonable to assess drug consumption, unless the level of consumption was once per month in the last 12 months. Doubling the monthly consumption increases hair MDMA by around 1 ng/mg hair up to a level of 4 consumed tablets a month. It does not seem possible to draw definitive conclusions from higher concentrations in hair samples.